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牛胸腺提取物(TFX®)体外的免疫调节作用与其对丝裂原激活蛋白激酶表达的影响有关。

Immunoregulatory actions of calf thymus extract (TFX®) in vitro in relation to its effect on expression of mitogen activated protein kinases.

机构信息

Laboratory of Immunobiology, Hirszfeld Institute of Immunology and Experimental Therapy, Wrocław, Poland.

Laboratory of Immunobiology, Hirszfeld Institute of Immunology and Experimental Therapy, Wrocław, Poland.

出版信息

Int Immunopharmacol. 2023 May;118:109995. doi: 10.1016/j.intimp.2023.109995. Epub 2023 Mar 23.

Abstract

The in vitro immunotropic actions of a calf thymus extract - thymus factor X (TFX®) preparation were investigated. The preparation did not lower the viability of the A549 epithelial cell line and mouse bone marrow cells in the investigated concentration range. TFX® exhibited a co-stimulatory action of concanavalin A (Con A)-induced mouse thymocyte proliferation and partially restored the mitogen-induced proliferation capability of mouse thymocytes exposed to hydrocortisone (HC). The preparation also inhibited Herpes virus-1 (HSV-1) replication in A549 cells when preincubated with the virus and when added to the infected cells. In addition, it weakly inhibited lipopolysaccharide (LPS)-induced TNF α, IL-1β and IL-6 by the THP-1 monocyte cell line. The determination of mitogen activated protein kinase (MAPK) expression in Jurkat T cells revealed strong increases in ERK-2 kinase and p38α subunits. In WEHI 231 immature B cells, TFX® elevated p38α, and had a particularly strong elevating effect on p38γ. In HL-60 myeloblastic cells, the expression of p38α, β and γ was not detectable, almost blocked for p38δ and JNK, but accompanied by an increase in ERK-1. In turn, the effects of TFX® in J744E macrophages resulted in a strong increase in p38γ expression, moderate elevations of ERK and a drop in p38δ. Significant increases in MAPK expression were also found in cells from the lymphoid organs. In the bone marrow cell population, p38α, β and γ, in thymocytes p38α, γ and δ, and in splenocytes p38β and γ, subunit expression was elevated. We conclude that the changes in MAPK expression may be attributed to cell maturation and differentiation, and explain the beneficial therapeutic effects of TFX®.

摘要

研究了小牛胸腺提取物-胸腺因子 X(TFX®)制剂的体外免疫调节作用。在研究的浓度范围内,该制剂不会降低 A549 上皮细胞系和小鼠骨髓细胞的活力。TFX®表现出伴刀豆球蛋白 A(Con A)诱导的小鼠胸腺细胞增殖的协同作用,并部分恢复了暴露于氢化可的松(HC)的有丝分裂原诱导的小鼠胸腺细胞增殖能力。该制剂还在与病毒预孵育和加入感染细胞时抑制 A549 细胞中的单纯疱疹病毒 1(HSV-1)复制。此外,它还可弱抑制脂多糖(LPS)诱导的 THP-1 单核细胞系产生的 TNF-α、IL-1β和 IL-6。Jurkat T 细胞中丝裂原激活蛋白激酶(MAPK)表达的测定显示 ERK-2 激酶和 p38α 亚基的强烈增加。在 WEHI 231 未成熟 B 细胞中,TFX®升高了 p38α,并对 p38γ具有特别强烈的升高作用。在 HL-60 髓样细胞中,p38α、β和γ的表达不可检测,p38δ和 JNK 几乎被阻断,但 ERK-1 增加。反过来,TFX®在 J744E 巨噬细胞中的作用导致 p38γ表达的强烈增加,ERK 的适度升高和 p38δ的下降。在淋巴细胞器官的细胞中也发现了 MAPK 表达的显著增加。在骨髓细胞群体中,p38α、β和γ,在胸腺细胞中 p38α、γ和 δ,以及在脾细胞中 p38β和 γ,亚基表达增加。我们得出结论,MAPK 表达的变化可能归因于细胞成熟和分化,并解释了 TFX®的有益治疗效果。

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